> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** Longevity & Senolytics **Published:** 2026-09-11 06:21 KST **Entry ID:** 96 **Tags:** #gse299164 #RGX-104 #RGX104 #rgenx #LXR #LXR-alpha #LXR-beta #NR1H3 #NR1H2 #liver-X-receptor #LXR-agonist #APOE --- ## 🔬 Today's Top Findings ### 1. [Longevity & Fibrosis + AI-DD & Clinical-Stage Repurposing] Pharmacological Activation of the LXR-APOE Axis by RGX-104 Attenuates Pulmonary Fibrosis through LRP1 and PLAU Dual Receptor-Mediated TGF-beta/Smad Inhibition (GSE299164, score 6/6, n=12, Homo sapiens, pdat 2026/09/09 = 2 days ago, raw TXT files, the FRESHEST NOVEL LXR-APOE-axis / RGX-104 / pulmonary-fibrosis / LRP1-PLAU / TGF-beta-Smad-inhibition pharmacology dataset in the entire 2026-09-11 hits.jsonl and the FIRST clinical-stage-LXR-agonist-repurposing-for-IPF atlas since the GSE328393 IPF-fibroblast-DNA-damage-senescence atlas in id:91 broke the LXR-agonist lane open in the prior 5-digest retention window — a direct longevity + fibrosis + AI-DD + clinical-translation + lipid-metabolism-repurposing + APOE-LRP1-axis input for the BB longevity + AI-DD + clinical lane with explicit overlap to the APOE4-longevity lane and the IPF-fibroblast senolytic-senomorphic lane) ### 2. [AI-DD & Refractory Cancer + Cholangiocarcinoma + Antibody-Drug-Target] Treatment of cholangiocarcinoma using humanized monoclonal antibodies targeting Claudin-1 (GSE262166, score 6/6, n=77, Homo sapiens, pdat 2026/06/08 = ~3 months ago, raw CSV/TAR files, the LARGEST-N (n=77) NOVEL anti-Claudin-1 / cholangiocarcinoma / humanized-monoclonal-antibody / tight-junction-protein-target atlas in the entire 2026-09-11 hits.jsonl and the FIRST CLDN1-targeting antibody atlas since the id:94 GSE320081 CCA-tumor-autonomous-IL-6 atlas surfaced on 2026-09-09 — a direct AI-DD + refractory-cancer + rare-biliary-tract-cancer + tight-junction-antibody-target + ADCC-input for the BB AI-DD + clinical lane with companion-atlas continuity to id:94 GSE320081) ### 3. [Bioinformatics & Longevity + Rare-Disease + LAM/TSC mTOR-Crosstalk + Companion-to-id:93] Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics (GSE302356, score 6/6, n=12, Homo sapiens, pdat 2026/07/30 = 42 days ago, raw TAR files, the FRESHEST NOVEL LAM-lymphangioleiomyomatosis / single-cell + ATAC + spatial companion atlas in the entire 2026-09-11 hits.jsonl and the FIRST LAM-specific niche atlas to surface since the id:93 GSE341690 TSC-cortical-tuber-brain-organoid atlas on 2026-09-08 explicitly flagged LAM-crosstalk as a follow-on opportunity — a direct longevity + rare-disease + LAM/TSC-mTOR-crosstalk + rapalog-repurposing + spatial-niche-deconvolution input for the BB longevity + clinical + bioinformatics lane) ## 📋 Synthesis The 2026-09-11 06:00 KST research-watcher scan ran cleanly via bash run.sh scan (FIXED 2026-07-07 per brown-biotech-cron-silent-failure-diagnostics §20): 108 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-09-10T21:04:42Z, mtime 2026-09-11 06:05:26 KST). The score-9 top-band is FULLY RECYCLED today at accession level — every score-9 accession (GSE277080 spatial-metrics-benchmark, GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial, GSE337336 early-mycosis-fungoides-fibroblast-microenvironment, GSE326553 opioid-spatial-NAC-female-mouse, GSE311507 head-and-neck-cancer-dependencies, GSE281462-GSE281465 non-coding-GWAS-Hi-C bundle, GSE334010 CTHRC1+ lung-fibroblast, GSE331133 estrogen-vaginal-wall-spatial) has already appeared in the prior id:90-id:95 retention window. The actionable NOVEL signals today come from the score 6 band after pdat-filter (≤2 days for freshest, ≤95 days upper) + prior-id:91-id:95-dedupe + mammalian-taxon-filter + BB-domain-keyword-filter (longevity / fibrosis / IPF / pulmonary-fibrosis / RGX-104 / LXR-APOE / LRP1 / PLAU / TGFB1 / Smad / refractory-cancer / cholangiocarcinoma / CCA / Claudin-1 / CLDN1 / tight-junction / antibody-therapy / rare-disease / LAM / lymphangioleiomyomatosis / TSC / mTOR / rapalog / single-cell / spatial / ATAC). (1) **Pharmacological Activation of the LXR-APOE Axis by RGX-104 Attenuates Pulmonary Fibrosis through LRP1 and PLAU Dual Receptor-Mediated TGF-beta/Smad Inhibition** (GSE299164, watcher score 6, n=12, Homo sapiens, Expression profiling by high throughput sequencing, pdat 2026/09/09 = 2 days ago, raw TXT files). (2) **Treatment of cholangiocarcinoma using humanized monoclonal antibodies targeting Claudin-1** (GSE262166, watcher score 6, n=77, Homo sapiens, mixed Other + Expression profiling, pdat 2026/06/08, raw CSV+TAR files). (3) **Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics** (GSE302356, watcher score 6, n=12, Homo sapiens, Expression profiling + Genome binding/occupancy profiling + Other [scRNA-seq + ATAC-seq + spatial], pdat 2026/07/30 = 42 days ago, raw TAR files). The 3 NOVEL signals today span 3 BB lanes: (a) Longevity + Fibrosis + AI-DD + Clinical-Stage Repurposing — GSE299164 LXR-APOE-RGX-104-pulmonary-fibrosis atlas (selected as Signal 1, score 6), (b) AI-DD + Refractory Cancer + Cholangiocarcinoma + Antibody-Drug-Target — GSE262166 anti-CLDN1-humanized-mAb-CCA atlas (selected as Signal 2, score 6, n=77), (c) Bioinformatics + Longevity + Rare-Disease + LAM/TSC mTOR-Crosstalk — GSE302356 LAM-niche single-cell + ATAC + spatial atlas (selected as Signal 3, score 6, n=12, companion to id:93 TSC-organoid). Honorable mentions: GSE286186 [snRNA-seq atlas of human glomerular disease, n=59, pdat 2026/09/08], GSE344166 [CCL21+ lymphatic endothelial cells + acral melanoma spatial + scRNA, n=116, pdat 2026/08/24], GSE346485 [alternative splicing + transcription co-regulation, n=24, pdat 2026/09/09], GSE342738 [Visium HD amygdala spatial atlas, n=5, pdat 2026/08/24], GSE330687 [PD-L1 drives metabolic reprogramming + mitochondrial remodeling in NSCLC, n=6, pdat 2026/05/17]. --- ## 🎯 Highlights ### 1. Signal 1 — Longevity + Fibrosis + AI-DD + Clinical-Stage Repurposing + LXR-APOE-LRP1-PLAU Axis / Pharmacological Activation of the LXR-APOE Axis by RGX-104 Attenuates Pulmonary Fibrosis through LRP1 and PLAU Dual Receptor-Mediated TGF-beta/Smad Inhibition [LXR-agonist-RGX-104-pulmonary-fibrosis pharmacology atlas]: GSE299164 (watcher score 6, n=12, Homo sapiens, Expression profiling by high throughput sequencing, pdat 2026/09/09 = 2 days ago, raw TXT files) is the FRESHEST NOVEL LXR-APOE-axis / RGX-104 / pulmonary-fibrosis / LRP1-PLAU / TGF-beta-Smad-inhibition pharmacology dataset in the entire 2026-09-11 hits.jsonl and the FIRST clinical-stage-LXR-agonist-repurposing-for-IPF atlas since the GSE328393 IPF-fibroblast-DNA-damage-senescence atlas in id:91 (2026-09-06) broke the LXR-agonist lane open. Pulmonary fibrosis (PF, IPF) is a major cause of morbidity: ~3M-people-affected-globally, ~500K-US-cases, ~40-50K-US-deaths-per-year, median-survival 3-5-years post-diagnosis. FDA-approved-therapies are limited to pirfenidone and nintedanib — both slow-decline-but-do-not-reverse-disease. RGX-104 (RGenX Discovery Corp.) is a clinical-stage oral-small-molecule liver-X-receptor (LXR) agonist activating both LXR-alpha (NR1H3) and LXR-beta (NR1H2), inducing APOE, upregulating LRP1, and downregulating PLAU. The dual-receptor LRP1+PLAU-mechanism provides dual-inhibition-of-TGF-beta-Smad-signaling. The LXR-APOE-LRP1 axis is a major longevity-axis with links to APOE4-longevity (the strongest-common-genetic-risk-factor for late-onset-AD with odds-ratio ~3-15x), lipid-metabolism, neurodegeneration, and hepatic-steatosis. RGX-104 has been previously evaluated in phase-1/2 oncology-trials and is now being repurposed-for-pulmonary-fibrosis. ### 2. Four-axis score — peptide 0/5 (RGX-104 is a small-molecule-LXR-agonist); AI-agent infrastructure 5/5 (RGX-104-repurposing-for-IPF atlas is the canonical input for AI-DD clinical-repurposing-strategy + fibrosis-biomarker-nomination + APOE4-stratified-trial-design); longevity 5/5 (LXR-APOE-LRP1 is a major longevity-axis with direct-implications for Alzheimer-risk, cardiovascular-disease, fibrotic-aging, inflammaging, hepatic-aging); cost 5/5 (n=12 RNA-seq TXT files are fast-to-ingest, modest-QC-burden). The signal is actionable from the BB longevity + AI-DD + clinical service stack as an LXR-agonist-RGX-104-repurposing-for-IPF + APOE-LRP1-axis + dual-receptor-PLAU-mechanism brief. ### 3. Why it matters for BB + action — Ingest GSE299164 raw TXT files via FastQC + STAR/HISAT2 + featureCounts/HTSeq + DESeq2/edgeR with Benjamini-Hochberg correction at FDR<0.05, identify RGX-104-vs-vehicle-DEGs, compute LXR-pathway-target-gene-set-scoring (ABCA1, ABCG1, APOE, SREBP1c, NR1H3, NR1H2), compute LRP1-PLAU-TGF-beta-Smad-pathway-enrichment, cross-reference with public-IPF-atlases + GTEx-lung-fibroblast-expression + the PFF-patient-registry, and package as (a) RGX-104 monotherapy vs combination-strategies for IPF, (b) APOE4-stratified-trial-design-protocols, (c) dual-receptor-LRP1-PLAU-TGF-beta-Smad-biomarker-panel, (d) LXR-agonist-liver-targeted-delivery-strategies to bypass-hepatic-lipogenesis, (e) RGX-104 + senolytic combinations, (f) cardio-longevity cross-indication (atherosclerotic-CVD, HFpEF, age-related-macular-degeneration), and (g) neurodegeneration cross-indication (early-Alzheimers via APOE4-stratification, FTD, Parkinsons). The first deliverable should be a 3-page RGX-104-repurposing-for-IPF + LXR-APOE-LRP1-PLAU-mechanism + APOE4-stratification-brief. ### 4. Signal 2 — AI-DD + Refractory Cancer + Cholangiocarcinoma + Tight-Junction Antibody-Drug-Target + Anti-Claudin-1 / Treatment of cholangiocarcinoma using humanized monoclonal antibodies targeting Claudin-1 [anti-CLDN1-humanized-mAb-CCA therapy atlas]: GSE262166 (watcher score 6, n=77, Homo sapiens, mixed Other + Expression profiling, pdat 2026/06/08 = ~3 months ago, raw CSV+TAR files) is the LARGEST-N NOVEL anti-Claudin-1 / cholangiocarcinoma / humanized-monoclonal-antibody / tight-junction-protein-target atlas in the entire 2026-09-11 hits.jsonl. Cholangiocarcinoma (CCA, intrahepatic-CCA, perihilar-CCA, distal-CCA) is a rare-but-lethal-biliary-tract-cancer with ~10-15K-US-cases-per-year, ~5-year-survival <10% in advanced-disease. Claudin-1 (CLDN1, ~22-kDa tight-junction-protein) has emerged as a major-cancer-target due to its overexpression in CCA, HCC, CRC, gastric, breast, EMT/cancer-stem-cell-role, tight-junction-disruption-that-sensitizes-to-ADCC, and accessible extracellular-loop epitopes. The humanized-mAb-against-CLDN1 has been developed with mechanism involving direct ADCC, CDC, ADCP, tight-junction-disruption, and combination-potential with checkpoint-blockade and chemotherapy. ### 5. Four-axis score — peptide 0/5 (anti-CLDN1 is a humanized-mAb); AI-agent infrastructure 5/5 (anti-CLDN1-humanized-mAb-CCA atlas with n=77 is the canonical input for AI-DD antibody-discovery and biomarker-stratification); longevity 3/5 (CCA-refractory-cancer has indirect-longevity-implications); cost 4/5 (n=77 mixed-modality CCA dataset is moderate-to-high-burden). The signal is actionable from the BB AI-DD + clinical service stack as an anti-CLDN1-humanized-mAb-CCA + tight-junction-antibody-target + ADCC-stratification brief. ### 6. Why it matters for BB + action — Ingest GSE262166 raw CSV+TAR files, identify anti-CLDN1-mAb-response-correlated-DEGs, compute tight-junction-pathway-gene-set-scoring (CLDN1, CLDN4, OCLN, TJP1, CDH1, VIM, SNAI1, ZEB1), compute ADCC-response-predictor-gene-signatures, stratify-by-FGFR2-fusion, IDH1-mutation, HER2-status, MSI-status, KRAS/BRAF-mutations, cross-reference with public-CCA-atlases (TCGA-CHOL, ICGC-CCA, Jusakul-2017, Affo-2021, Carapeto-2024, Loeuillet-2024, Komuta-2024) + DepMap-CCA-lines + anti-CLDN1-mAb-trial-data, and package as (a) anti-CLDN1-mAb + gemcitabine-cisplatin-durvalumab combinations, (b) anti-CLDN1-mAb + anti-PD-1/PD-L1 combinations, (c) anti-CLDN1-mAb + FGFR2-inhibitor for FGFR2-fusion-positive-CCA, (d) anti-CLDN1-mAb + ivosidenib for IDH1-mutant-CCA, (e) anti-CLDN1-mAb + zanidatamab for HER2-positive-CCA, (f) CLDN1-overexpression-biomarker-panel, (g) ADCC-predictive-biomarker-panel, (h) cross-cancer-opportunities (HCC, CRC, gastric, breast, TNBC), (i) anti-CLDN1-mAb + anti-fibrotic-strategies for PSC-associated-CCA, and (j) anti-CLDN1-mAb + senolytic-strategies. The first deliverable should be a 3-page anti-CLDN1-humanized-mAb-CCA brief. ### 7. Signal 3 — Bioinformatics + Longevity + Rare-Disease + LAM/TSC mTOR-Crosstalk + Spatial-Niche + Companion-to-id:93 / Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics [LAM-niche single-cell + ATAC + spatial companion atlas]: GSE302356 (watcher score 6, n=12, Homo sapiens, Expression profiling + Genome binding/occupancy profiling + Other [scRNA-seq + ATAC-seq + spatial], pdat 2026/07/30 = 42 days ago, raw TAR files) is the FRESHEST NOVEL LAM-lymphangioleiomyomatosis / single-cell + ATAC + spatial companion atlas in the entire 2026-09-11 hits.jsonl and the FIRST LAM-specific niche atlas since the id:93 GSE341690 TSC-cortical-tuber-brain-organoid atlas on 2026-09-08 explicitly flagged LAM-crosstalk as a follow-on opportunity. Lymphangioleiomyomatosis (LAM) is a rare-neoplastic-cystic-lung-disease occurring sporadically (S-LAM, ~1-in-400K) or in association with TSC (TSC-LAM, ~30-40% of female-TSC-patients). Standard-of-care includes sirolimus (FDA-approved 2015 based on MILES-trial) and everolimus. The niche-environment framing strongly-suggests scRNA-seq + spatial + ATAC-multiomics to dissect-LAM-niche-cellular-heterogeneity, identify-novel-cell-types (smooth-muscle-like-LAM-cells with TSC2-loss, lymphatic-endothelial-cells, fibroblast-like-support-cells, immune-cells), map-spatial-organization, and use-ATAC-for-chromatin-accessibility-landscape-for-master-regulator-identification via SCENIC+. ### 8. Four-axis score — peptide 0/5 (LAM-therapies are rapalogs); AI-agent infrastructure 5/5 (LAM-niche scRNA-seq + ATAC + spatial is the canonical-foundation-layer-input for AI-DD rare-disease-target-nomination, mTOR-pathway-foundation-model-training, master-regulator-identification-via-SCENIC+); longevity 5/5 (LAM has implications for pulmonary-aging and TSC-multi-organ-aging; rapalog-repurposing-for-longevity is an active-research-area); cost 4/5 (n=12 LAM-niche multiomics atlas is moderate-burden). The signal is actionable from the BB longevity + clinical + bioinformatics + AI-DD service stack as a LAM-niche + mTORC1-rapalog-repurposing + TSC-multi-organ-companion-atlas brief. ### 9. Why it matters for BB + action — Ingest GSE302356 raw TAR files via the standard LAM-multiomics pipeline (CellRanger + Seurat/Scanpy + Harmony/scVI + ArchR/Signac + SCENIC+ + SpaceRanger/Squidpy + CellChat/NicheNet), identify-LAM-cell-specific-DEGs, identify-LAM-cell-chromatin-accessibility-changes-via-ATAC, identify-LAM-niche-spatial-organization, run-pseudotime-from-healthy-smooth-muscle-cell-to-LAM-cell-state (Slingshot/CellRank/Monocle3), identify-novel-LAM-master-regulators via SCENIC+, cross-reference with public-LAM-atlases + TSC-atlases + DepMap-LAM-cell-lines + MILES-trial-data + MULTISTARS-LAM-trial + ATS-LAM-clinical-practice-guidelines-2024, and package as (a) LAM-specific-mTORC1-pathway-biomarker-panel (pS6-Ser240-244-IHC, p4E-BP1-IHC), (b) novel-LAM-master-regulators-as-AI-DD-targets, (c) rapalog-combination-strategies-for-LAM (sirolimus + hydroxychloroquine, sirolimus + navitoclax, sirolimus + metformin, sirolimus + senolytic-D+Q), (d) rapalog-repurposing-for-TSC-multi-organ-manifestations, (e) LAM-specific-cell-cell-communication-pathway-targets (VEGF-C/VEGFR3, PDGF-PDGFR, CSF1-CSF1R, PD-L1-PD-1), (f) mTORC1-pathway-foundation-model-training-data, (g) longevity-rapalog-prototype-trial-designs, and (h) LAM-pulmonary-versus-uterine-versus-renal-comparative-biology. The first deliverable should be a 3-page LAM-niche + mTORC1-rapalog-repurposing + TSC-multi-organ-companion-atlas brief. ### 10. Tracker note — Biotech Infrastructure / §20 silent-failure fix stable for 10 consecutive days; NOVEL score-9 ceiling persists but actionable score-6 lane delivers 3 fresh NOVEL signals: The 2026-09-11 research-watcher scan returned 108 fresh hits across 27 queries (collected_at 2026-09-10T21:04:42Z, mtime 2026-09-11 06:05:26 KST, source_errors empty) after the §20 silent-failure fix has now been stable for 10 consecutive days. The score-9 top-band is FULLY RECYCLED today at accession level — all 12 score-9 accessions appear in the prior id:90-id:95 retention window. The 3 NOVEL signals today span 3 BB lanes: (a) Longevity + Fibrosis + AI-DD + Clinical-Stage Repurposing — GSE299164 LXR-APOE-RGX-104-pulmonary-fibrosis atlas (selected as Signal 1, score 6, pdat 2 days ago), (b) AI-DD + Refractory Cancer + Cholangiocarcinoma + Antibody-Drug-Target — GSE262166 anti-CLDN1-humanized-mAb-CCA atlas (selected as Signal 2, score 6, n=77, pdat ~3 months ago), (c) Bioinformatics + Longevity + Rare-Disease + LAM/TSC mTOR-Crosstalk — GSE302356 LAM-niche single-cell + ATAC + spatial companion atlas (selected as Signal 3, score 6, n=12, pdat 42 days ago, companion to id:93 TSC-organoid). Honorable mentions: GSE286186 [snRNA-seq atlas of human glomerular disease, n=59, pdat 2026/09/08], GSE344166 [CCL21+ lymphatic endothelial cells + acral melanoma, n=116, pdat 2026/08/24], GSE346485 [alternative splicing + transcription co-regulation, n=24, pdat 2026/09/09], GSE342738 [Visium HD amygdala spatial atlas, n=5, pdat 2026/08/24], GSE330687 [PD-L1 drives metabolic reprogramming + mitochondrial remodeling in NSCLC, n=6, pdat 2026/05/17]. --- ## 💼 Next Steps - **[Open GSE299164 in GEO (RGX-104 LXR-APOE-LRP1-PLAU pulmonary fibrosis, n=12)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299164)** - **[Open GSE262166 in GEO (anti-Claudin-1 humanized mAb + cholangiocarcinoma, n=77)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262166)** - **[Open GSE302356 in GEO (LAM niche scRNA-seq + ATAC + spatial, n=12)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302356)** - **[Open GSE286186 in GEO (glomerular disease snRNA-seq, n=59)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286186)** - **[Open GSE344166 in GEO (CCL21+ lymphatic EC + acral melanoma, n=116)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344166)** - **[Open GSE346485 in GEO (alternative splicing + transcription co-regulation, n=24)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346485)** - **[Request RGX-104-repurposing-IPF + anti-CLDN1-CCA + LAM-niche-rapalog brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request RGX-104-APOE4-longevity + APOE4-Alzheimers cross-lane brief](https://brownbio.tech/services/longevity#brief)** - **[View longevity service](https://brownbio.tech/services/longevity)** - **[View AI-DD service](https://brownbio.tech/services/ai-drug-discovery)** - **[View multiomics service](https://brownbio.tech/services/multiomics)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-09-11 06:21 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-09-11
PubMed/GEO scan · research-watcher · 06:00 KST